Article

Polycystic kidney disease and the renal cilium (Review Article)

Monash Immunology and Stem Cell Laboratories (MISCL), Monash University, Melbourne Victoria, Australia
Nephrology (Impact Factor: 1.69). 11/2007; 12(6):559 - 564. DOI: 10.1111/j.1440-1797.2007.00869.x

ABSTRACT Polycystic kidney disease (PKD) is a common genetic condition characterized by the formation of fluid-filled cysts in the kidney. Mutations affecting several genes are known to cause PKD and the protein products of most of these genes localize to an organelle called the renal cilium. Renal cilia are non-motile, microtubule-based projections located on the apical surface of the epithelial cells that form the tubules and ducts of the kidney. With the exception of intercalated cells, each epithelial cell bears a single non-motile cilium that projects into the luminal space where it is thought to act as a flow sensor. The detection of fluid flow through the kidney by the renal cilium is hypothesized to regulate a number of pathways responsible for the maintenance of normal epithelial phenotype. Defects of the renal cilium lead to cyst formation, caused primarily by the dedifferentiation and over-proliferation of epithelial cells. Here we discuss the role of renal cilia and the mechanisms by which defects of this organelle are thought to lead to PKD.

0 Bookmarks
 · 
65 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Almost all mammalian cells carry one primary cilium that functions as a biosensor for chemical and mechanical stimuli. Genetic damages that compromise cilia formation or function cause a spectrum of disorders referred to as ciliapathies. Recent studies have demonstrated that some pharmacological agents and extracellular environmental changes can alter primary cilium length. Renal injury is a well-known example of an environmental insult that triggers cilia length modification. Lithium treatment causes primary cilia to extend in several cell types including neuronal cells;this phenomenon is likely independent of glycogen synthase kinase-3β inhibition. In renal epithelial cell lines, deflection of the primary cilia by fluid shear shortens them by reducing the intracellular cyclic AMP level, leading to a subsequent decrease in mechanosensitivity to fluid shear. Primary cilium length is also influenced by the dynamics of actin filaments and microtubules through the levels of soluble tubulin in the cytosol available for primary cilia extension. Thus, mammalian cells can adapt to the extracellular environment by modulating the primary cilium length, and this feedback system utilizing primary cilia might exist throughout the mammalian body. Further investigation is required concerning the precise molecular mechanisms underlying the control of primary cilium length in response to environmental factors.
    Acta medica Okayama 10/2011; 65(5):279-85. · 0.65 Impact Factor
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Renal primary cilia are microscopic sensory organelles found on the apical surface of epithelial cells of the nephron and collecting duct. They are based upon a microtubular cytoskeleton, bounded by a specialized membrane, and contain an array of proteins that facilitate their assembly, maintenance and function. Cilium-based signalling is important for the control of epithelial differentiation and has been implicated in the pathogenesis of various cystic kidney diseases and in renal repair. As such, visualising renal primary cilia and understanding their composition has become an essential component of many studies of inherited kidney disease and mechanisms of epithelial regeneration. Primary cilia were initially identified in the kidney using electron microscopy and this remains a useful technique for the high resolution examination of these organelles. New reagents and techniques now also allow the structure and composition of primary cilia to be analyzed in detail using fluorescence microscopy. Primary cilia can be imaged in situ in sections of kidney, and many renal-derived cell lines produce primary cilia in culture providing a simplified and accessible system in which to investigate these organelles. Here we outline microscopy-based techniques commonly used for studying renal primary cilia.
    Nephrology 12/2012; · 1.69 Impact Factor

Full-text

View
39 Downloads
Available from
Jun 1, 2014